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https://www.readbyqxmd.com/read/28808972/chromosome-conformation-capture-for-research-on-innate-antiviral-immunity
#1
Yoon Jung Kim, Tae Hoon Kim
Chromosome conformation capture (3C) technology has revolutionized our knowledge on chromatin folding and nuclear organization. This cis-loop detection approach can be used to identify candidate regulatory elements interacting with target gene of interest. This chapter introduces the application of 3C technique to investigate a dynamic alteration in the chromosome folding structure or genomic architecture resulting from interaction changes between the enhancer and its target gene. Innate antiviral immunity is one of the well-known gene induction systems, involving rapid first-line response to virus or pathogen to trigger gene expression changes in order to protect cells and to limit further infection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28805829/lineage-specific-dynamic-and-pre-established-enhancer-promoter-contacts-cooperate-in-terminal-differentiation
#2
Adam J Rubin, Brook C Barajas, Mayra Furlan-Magaril, Vanessa Lopez-Pajares, Maxwell R Mumbach, Imani Howard, Daniel S Kim, Lisa D Boxer, Jonathan Cairns, Mikhail Spivakov, Steven W Wingett, Minyi Shi, Zhixin Zhao, William J Greenleaf, Anshul Kundaje, Michael Snyder, Howard Y Chang, Peter Fraser, Paul A Khavari
Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer-promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer-promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28802249/high-resolution-mapping-of-chromatin-conformation-in-cardiac-myocytes-reveals-structural-remodeling-of-the-epigenome-in-heart-failure
#3
Manuel Rosa-Garrido, Douglas J Chapski, Anthony D Schmitt, Todd H Kimball, Elaheh Karbassi, Emma Monte, Enrique Balderas, Matteo Pellegrini, Tsai-Ting Shih, Elizabeth Soehalim, David A Liem, Peipei Ping, Niels J Galjart, Shuxun Ren, Yibin Wang, Bing Ren, Thomas M Vondriska
Background -Cardiovascular disease is associated with epigenomic changes in the heart, however the endogenous structure of cardiac myocyte chromatin has never been determined. Methods -To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype...
August 11, 2017: Circulation
https://www.readbyqxmd.com/read/28794204/chromosome-topology-guides-the-drosophila-dosage-compensation-complex-for-target-gene-activation
#4
Tamás Schauer, Yad Ghavi-Helm, Tom Sexton, Christian Albig, Catherine Regnard, Giacomo Cavalli, Eileen Em Furlong, Peter B Becker
X chromosome dosage compensation in Drosophila requires chromosome-wide coordination of gene activation. The male-specific lethal dosage compensation complex (DCC) identifies and binds to X-chromosomal high-affinity sites (HAS) from which it boosts transcription. A sub-class of HAS, PionX sites, represent first contacts on the X. Here, we explored the chromosomal interactions of representative PionX sites by high-resolution 4C and determined the global chromosome conformation by Hi-C in sex-sorted embryos. Male and female X chromosomes display similar nuclear architecture, concordant with clustered, constitutively active genes...
August 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28792605/single-cell-hi-c-bridges-microscopy-and-genome-wide-sequencing-approaches-to-study-3d-chromatin-organization
#5
REVIEW
Sergey V Ulianov, Kikue Tachibana-Konwalski, Sergey V Razin
Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture (3C)-based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes...
August 9, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28775067/running-training-experience-attenuates-disuse-atrophy-in-fast-twitch-skeletal-muscles-of-rats
#6
Keisuke Nakamura, Ikumi Ohsawa, Ryo Masuzawa, Ryotaro Konno, Atsuya Watanabe, Fuminori Kawano
Responsiveness to physiological stimuli, such as exercise and muscular inactivation, differs in individuals. However, the mechanisms responsible for these individual differences remain poorly understood. We tested whether a prior experience of exercise training affects the responses of skeletal muscles to unloading. Young rats were assigned to perform daily running training using a treadmill for 8 weeks. After an additional 8 weeks of normal habitation, the rats were hindlimb unloaded by tail suspension for 1 week...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28771695/challenges-for-visualizing-three-dimensional-data-in-genomic-browsers
#7
REVIEW
Mike Goodstadt, Marc A Marti-Renom
Genomic interactions reveal the spatial organization of genomes and genomic domains, which is known to play key roles in cell function. Physical proximity can be represented as two-dimensional heat maps or matrices. From these, three-dimensional (3D) conformations of chromatin can be computed revealing coherent structures that highlight the importance of non-sequential relationships across genomic features. Mainstream genomic browsers have been classically developed to display compact, stacked tracks based on a linear, sequential, per-chromosome coordinate system...
August 3, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28767037/cryo-em-structure-of-the-saga-and-nua4-coactivator-subunit-tra1-at-3-7-angstrom-resolution
#8
Luis Miguel Diaz-Santin, Natasha Lukoyanova, Emir Aciyan, Alan Cm Cheung
Coactivator complexes SAGA and NuA4 stimulate transcription by post-translationally modifying chromatin. Both complexes contain the Tra1 subunit, a highly conserved 3744-residue protein from the Phosphoinositide 3-Kinase-related kinase (PIKK) family and a direct target for multiple sequence-specific activators. We present the Cryo-EM structure of Saccharomyces cerevsisae Tra1 to 3.7 Å resolution, revealing an extensive network of alpha-helical solenoids organized into a diamond ring conformation and is strikingly reminiscent of DNA-PKcs, suggesting a direct role for Tra1 in DNA repair...
August 2, 2017: ELife
https://www.readbyqxmd.com/read/28764714/testis-specific-histone-2b-is-associated-with-sperm-chromatin-dynamics-and-bull-fertility-a-pilot-study
#9
Naseer A Kutchy, Ana Velho, Erika S B Menezes, Marie Jacobsen, Giselle Thibaudeau, Robert W Wills, Arlindo Moura, Abdullah Kaya, Andy Perkins, Erdogan Memili
BACKGROUND: Bull fertility is the degree of sperm's ability to fertilize and activate the egg and support embryo development, and this is critical for herd reproductive performance. We used the bull as a unique model organism for the study of male fertility because cattle genetics and physiology is similar to those of other mammals including humans. Moreover, reliable fertility data along with well-established in vitro systems are available for bovine. The objective of this original study was to ascertain evolutionary diversification and expression dynamics of Testis Specific Histone 2B (TH2B) in sperm from Holstein bulls with different fertility scores...
August 1, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28752814/a-matter-of-scale-and-dimensions-chromatin-of-chromosome-landmarks-in-the-fungi
#10
Allyson A Erlendson, Steven Friedman, Michael Freitag
Chromatin and chromosomes of fungi are highly diverse and dynamic, even within species. Much of what we know about histone modification enzymes, RNA interference, DNA methylation, and cell cycle control was first addressed in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus nidulans, and Neurospora crassa. Here, we examine the three landmark regions that are required for maintenance of stable chromosomes and their faithful inheritance, namely, origins of DNA replication, telomeres and centromeres...
July 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28751304/a-lipodystrophy-causing-lamin-a-mutant-alters-conformation-and-epigenetic-regulation-of-the-anti-adipogenic-mir335-locus
#11
Anja Oldenburg, Nolwenn Briand, Anita L Sørensen, Inswasti Cahyani, Akshay Shah, Jan Øivind Moskaug, Philippe Collas
Mutations in the Lamin A/C (LMNA) gene-encoding nuclear LMNA cause laminopathies, which include partial lipodystrophies associated with metabolic syndromes. The lipodystrophy-associated LMNA p.R482W mutation is known to impair adipogenic differentiation, but the mechanisms involved are unclear. We show in this study that the lamin A p.R482W hot spot mutation prevents adipogenic gene expression by epigenetically deregulating long-range enhancers of the anti-adipogenic MIR335 microRNA gene in human adipocyte progenitor cells...
July 27, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28742318/development-of-a-virtual-cell-model-to-predict-cell-response-to-substrate-topography
#12
Tiam Heydari, Maziar Heidari, Omid Mashinchian, Michal Wojcik, Ke Xu, Matthew John Dalby, Morteza Mahmoudi, Mohammad Reza Ejtehadi
Cells can sense and respond to changes in the topographical, chemical, and mechanical information in their environment. Engineered substrates are increasingly being developed that exploit these physical attributes to direct cell responses (most notably mesenchymal stem cells) and therefore control cell behavior toward desired applications. However, there are very few methods available for robust and accurate modeling that can predict cell behavior prior to experimental evaluations and this typically means that many cell test iterations are needed to identify best material features...
July 25, 2017: ACS Nano
https://www.readbyqxmd.com/read/28740156/mapping-the-dynamics-of-the-glucocorticoid-receptor-within-the-nuclear-landscape
#13
Martin Stortz, Diego M Presman, Luciana Bruno, Paolo Annibale, Maria V Dansey, Gerardo Burton, Enrico Gratton, Adali Pecci, Valeria Levi
The distribution of the transcription machinery among different sub-nuclear domains raises the question on how the architecture of the nucleus modulates the transcriptional response. Here, we used fluorescence fluctuation analyses to quantitatively explore the organization of the glucocorticoid receptor (GR) in the interphase nucleus of living cells. We found that this ligand-activated transcription factor diffuses within the nucleus and dynamically interacts with bodies enriched in the coregulator NCoA-2, DNA-dependent foci and chromatin targets...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28735859/computational-prediction-of-position-effects-of-apparently-balanced-human-chromosomal-rearrangements
#14
Cinthya J Zepeda-Mendoza, Jonas Ibn-Salem, Tammy Kammin, David J Harris, Debra Rita, Karen W Gripp, Jennifer J MacKenzie, Andrea Gropman, Brett Graham, Ranad Shaheen, Fowzan S Alkuraya, Campbell K Brasington, Edward J Spence, Diane Masser-Frye, Lynne M Bird, Erica Spiegel, Rebecca L Sparkes, Zehra Ordulu, Michael E Talkowski, Miguel A Andrade-Navarro, Peter N Robinson, Cynthia C Morton
Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities...
August 3, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28728680/at-the-base-of-colinear-hox-gene-expression-cis-features-and-trans-factors-orchestrating-the-initial-phase-of-hox-cluster-activation
#15
REVIEW
Roel Neijts, Jacqueline Deschamps
Hox genes are crucial players in the generation and pattering of the vertebrate trunk and posterior body during embryogenesis. Their initial expression takes place shortly after the establishment of the primitive streak, in the posterior-most part of the mouse embryo and is a determinant step for setting up the definitive Hox expression boundaries along the antero-posterior body axis. The developmental signals and epigenetic mechanisms underlying this early activation remained unsolved until recently. The development of novel embryo-derived model systems, combined with methods that examine chromatin status and chromosome conformation, led to deeper understanding of the process of Hox activation in the early embryo...
August 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28723903/automatic-analysis-and-3d-modelling-of-hi-c-data-using-tadbit-reveals-structural-features-of-the-fly-chromatin-colors
#16
François Serra, Davide Baù, Mike Goodstadt, David Castillo, Guillaume J Filion, Marc A Marti-Renom
The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three-dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, provide unprecedented insights in the spatial organization of genomes. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#17
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28722347/foxo3-longevity-interactome-on-chromosome-6
#18
Timothy A Donlon, Brian J Morris, Randi Chen, Kamal H Masaki, Richard C Allsopp, D Craig Willcox, Ayako Elliott, Bradley J Willcox
FOXO3 has been implicated in longevity in multiple populations. By DNA sequencing in long-lived individuals, we identified all single nucleotide polymorphisms (SNPs) in FOXO3 and showed 41 were associated with longevity. Thirteen of these had predicted alterations in transcription factor binding sites. Those SNPs appeared to be in physical contact, via RNA polymerase II binding chromatin looping, with sites in the FOXO3 promoter, and likely function together as a cis-regulatory unit. The SNPs exhibited a high degree of LD in the Asian population, in which they define a specific longevity haplotype that is relatively common...
July 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28720171/pacbio-assembly-of-a-plasmodium-knowlesi-genome-sequence-with-hi-c-correction-and-manual-annotation-of-the-sicavar-gene-family
#19
S A Lapp, J A Geraldo, J-T Chien, F Ay, S B Pakala, G Batugedara, J Humphrey, J D DeBARRY, K G Le Roch, M R Galinski, J C Kissinger
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features...
July 19, 2017: Parasitology
https://www.readbyqxmd.com/read/28716950/analysis-of-small-critical-regions-of-swi1-conferring-prion-formation-maintenance-and-transmission
#20
Stephanie Valtierra, Zhiqiang Du, Liming Li
Saccharomyces cerevisiae contains several prion elements, which are epigenetically transmitted as self-perpetuating protein conformations. One such prion is [SWI(+) ], whose protein determinant is Swi1, a subunit of the SWI/SNF chromatin-remodeling complex. We previously reported that [SWI(+) ] formation results in a partial loss-of-function phenotype of poor growth in non-glucose media and abolishment of multicellularity. We also showed that the first 38 amino acids of Swi1 propagated [SWI(+)]. We show here that a region as small as the first 32 amino acids of Swi1 (Swi11-32) can decorate [SWI(+)] aggregation and stably maintain and transmit [SWI(+)] independently of full-length Swi1...
July 17, 2017: Molecular and Cellular Biology
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